Department of Pharmacology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Nitric Oxide. 2011 Aug 1;25(2):102-7. doi: 10.1016/j.niox.2011.02.006. Epub 2011 Mar 4.
The distinctive function of nitric oxide (NO) in biology is to transmit cellular signals through membranes and regulate cellular functions in adjacent cells. NO conveys signals as a second messenger from a cell where NO is generated to contiguous cells in two ways; one is as gaseous molecule by free diffusion resulting in an activation of soluble guanylate cyclase (NO/cGMP pathway), and another form is by binding with a molecule such as cysteine or protein thiol through S-nitrosylation (SNO pathway). Both pathways transmit much of the biological influence of NO from cell where other messenger molecules but NO are confined, through the plasma membrane to the adjacent cells. Since SNO pathway cannot utilize free-diffusion mechanism to get through the membrane as the molecular size is significantly larger than NO molecule, it utilizes amino acid transporter to convey signals as a form of S-nitrosylated cysteine (CysNO). Although S-nitrosylated glutathione (GSNO) is the molecule which act as a determinant of the total S-nitrosothiol level in cell, transnitrosylation reaction from GSNO to CysNO is an initial requirement to pass through signal through the membrane. Thus, multiplexed combination of these steps and the regulatory factors involved in this system conform and modify the outcome from stimulus-response coupling via the SNO pathway.
一氧化氮(NO)在生物学中的独特功能是通过细胞膜传递细胞信号并调节相邻细胞的细胞功能。NO 作为一种第二信使,以两种方式从产生 NO 的细胞传递信号到相邻细胞:一种是通过自由扩散作为气态分子,导致可溶性鸟苷酸环化酶(NO/cGMP 途径)的激活,另一种形式是通过与半胱氨酸或蛋白巯基等分子结合通过 S-亚硝化(SNO 途径)。这两种途径都将 NO 从其他信使分子受限的细胞中的大部分生物学影响传递到相邻细胞,通过质膜传递。由于 SNO 途径的分子大小明显大于 NO 分子,因此不能利用自由扩散机制穿过细胞膜,它利用氨基酸转运蛋白将信号作为 S-亚硝基化半胱氨酸(CysNO)的形式传递。虽然 S-亚硝基化谷胱甘肽(GSNO)是细胞中总 S-亚硝基硫醇水平的决定因素,但从 GSNO 到 CysNO 的转亚硝基反应是穿过信号穿过细胞膜的初始要求。因此,这些步骤的多重组合以及涉及该系统的调节因子的组合和修改了通过 SNO 途径的刺激-反应偶联的结果。